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leukoaraiosis is associated with clinical symptom severity,poor neurological function prognosis and stroke recurrence in mild intracerebral hemorrhage:a prospective multi-center cohort study

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Neural Regeneration Research 2022年第4期17卷 819-823页

作者： Tian-Qi Xu Wei-Zhi Lin Yu-Lan Feng Fan-Xia Shen Jie Chen Wei-Wen Wu Xiao-Dong Zhu Lin Gu Yi Fu Department of Neurology Ruijin Hospital/Luwan BranchSchool of MedicineShanghai Jiao Tong UniversityShanghaiChina The Third Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine FuzhouFujian ProvinceChina Department of Neurology Minhang HospitalFudan UniversityShanghaiChina Department of Neurology Ruijin North HospitalShanghaiChina Department of Neurology Zhongshan Hospital Qingpu BranchFudan UniversityShanghaiChina Department of Neurology The First Hospital of JiaxingJiaxingZhejiang ProvinceChina Department of Rehabilitation Shanghai Ruijin Rehabilitation HospitalShanghaiChina

leukoaraiosis(LA)results from ischemic injury in small cerebral vessels,which may be attributable to decreased vascular density,reduced cerebrovascular angiogenesis,decreased cerebral blood flow,or microcirculatory dysfunction in the brain.In this study,we enrolled 357 patients with mild intracerebral hemorrhage(ICH)from five hospitals in China and analyzed the relationships between LA and clinical symptom severity at admission,neurological function prognosis at 3 months,and 1-year stroke recurrence.Patients were divided into groups based on Fazekas scale scores:no LA(n=83),mild LA(n=64),moderate LA(n=98)and severe LA(n=112).More severe LA,larger hematoma volume,and higher blood glucose level at admission were associated with more severe neurological deficit.More severe LA,older age and larger hematoma volume were associated with worse neurological function prognosis at 3 months.In addition,moderate-to-severe LA,admission glucose and symptom-free cerebral infarction were associated with 1-year stroke recurrence.These findings suggest that LA severity may be a potential marker of individual ICH vulnerability,which can be characterized by poor tolerance to intracerebral attack or poor recovery ability after ICH.Evaluating LA severity in patients with mild ICH may help neurologists to optimize treatment protocols.This study was approved by the Ethics Committee of Ruijin Hospital Affiliated to Shanghai Jiao Tong University(approval No.12)on March 10,2011.

关键词： clinical symptom severity functional dependence intracerebral hemorrhage leukoaraiosis modified Rankin scale National Institute Health of Stroke Scale prognosis stroke recurrence white matter hyperintensities

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DDAH2(-449 G/C) G allele is positively associated with leukoaraiosis in northeastern China: a double-blind, intergroup comparison, case-control study

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Neural Regeneration Research 2021年第8期16卷 1592-1597页

作者： Ying Fan Qiang Gao Jia-Xin Guan Lei Liu Ming Hong Li Jun Li Wang Hai-Feng Ding Li-Hong Jiang Bo-Yu Hou Mei Li Zhi-Qiang Song De-Qin Sun Chao-Qi Yan Lan Ma Department of Geriatrics The 2nd Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiang ProvinceChina Department of Geriatrics Tongling Municipal HospitalTonglingAnhui ProvinceChina Department of Cardiovascular Medicine Shanxi Cardiovascular HospitalTaiyuanShanxi ProvinceChina Physical Examination Center The 2nd Affiliated Hospital of Harbin Medical UniversityHarbinHeilongjiang ProvinceChina

Cerebrovascular endothelial dysfunction is involved in the progression of leukoaraiosis. Asymmetric dimethylarginine is a competitive inhibitor of nitric oxide, which is highly expressed in patients with leukoaraiosis. Dimethylarginine dimethylaminohydrolase(DDAH) is a hydrolytic enzyme that is primarily responsible for eliminating asymmetric dimethylarginine, and it plays a role in the pathogenesis of cardiovascular and cerebrovascular diseases. The DDAH2 subtype is expressed in organs rich in induced nitric oxide synthase, including the heart, the placenta, and the cerebral endothelium during cerebral ischemia, in the stress state, or under neurotoxicity. Overexpression of the DDAH2 gene can inhibit asymmetric dimethylarginine-induced peripheral circulating endothelial cell dysfunction. However, it is unknown whether this polymorphism regulates plasma asymmetric dimethylarginine levels in patients with leukoaraiosis. In this doubleblind study, we recruited 46 patients with leukoaraiosis and 46 healthy, matched controls. Plasma asymmetric dimethylarginine levels were determined using enzyme-linked immunoassays. Genomic DNA was isolated from whole blood samples, and polymerase chain reaction, Sma I restriction enzyme digestion, restriction fragment length polymorphisms, and agarose electrophoresis were used to detect DDAH2(-449 G/C) gene polymorphisms. The results revealed that 95.65% of leukoaraiosis patients had recessive genetic models(GG and CG), while 89.13% of healthy control subjects had dominant genetic models(CC and CG). There was a significant difference in the genotype composition ratio between leukoaraiosis patients and healthy controls(P = 0.0002). The frequency of G alleles in the leukoaraiosis patients(71.74%) was significantly higher than in healthy controls, whereas the frequency of C alleles was lower(χ~2 = 13.9580, P = 0.0002). Furthermore, asymmetric dimethylarginine concentrations in subjects with the GG genotype were significantly higher than in subjects with the CG and CC genotypes(Kruskal–

关键词： leukoaraiosis dimethylarginine dimethylaminohydrolase 2 gene polymorphism allele asymmetric dimethylarginine nitric oxide endothelial dysfunction cerebrovascular diseases clinical trial

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Lacunar infarction with leukoaraiosis may aggravate cognitive dysfunction

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Neural Regeneration Research 2011年第31期6卷 2446-2451页

作者： Dejin Sun Xueqin Zhang Penju Liu Jiechun Chen Jinxia Cao Aixia Zhuang Qinghong Zeng Shouqin Feng Yi Zhang Jiandong Jiang Department of Neurology Lianyungang Second People＇s Hospital （Lianyungang Hospital of Bengbu Medical College） Lianyungang 222023 Jiangsu Province China Department of Neurology Beijing Tongren Hospital Capital Medical University Beijing 100730 China Department of Neurology Beijing Anzhen Hospital Capital Medical University Beijing 100730 China Neurophysiological Room Lianyungang Second People＇s Hospital （Lianyungang Hospital of Bengbu Medical College） Lianyungang 222023 Jiangsu Province China Department of Radiology Lianyungang Second People＇s Hospital （Lianyungang Hospital of Bengbu Medical College） Lianyungang 222023 Jiangsu Province China

This study semi-quantitatively analyzed the effects of leukoaraiosis.Patients with moderate or severe lacunar infarction were found to exhibit low scores on the Montreal Cognitive Assessment Scale （F=12.02,P=0.000）,and prolonged P300 Cz2.0 latency （F=16.04,P=0.000）.Correlation analysis revealed that the occurrence of leukoaraiosis was negatively correlated with Montreal Cognitive Assessment scores （r=-0.416,P=0.000）,and positively correlated with P300 Cz2.0 latency （r=0.538,P=0.000）.These findings indicate that leukoaraiosis aggravates cognitive impairment in patients with lacunar infarction,such that more severe leukoaraiosis is associated with more severe cognitive decline.

关键词： lacunar infarction leukoaraiosis event-related potentials semi-quantitative analysis vascular cognitive impairment

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Cognitive Functional Impairment and Hemodynamic Changes in Patients with Symptomatic leukoaraiosis

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Journal of Behavioral and Brain Science 2022年第6期12卷 271-286页

作者： Yuanhao Chen Yujiao Lin Ying Bian Department of Neurology The Third Affiliated Hospital of Sun Yat-sen University Yuedong Hospital Meizhou China Ultrasonography Department The Fifth People’s Hospital of Shenyang Shenyang China

Objective: The pathogenesis of leukoaraiosis is still unclear. Many studies have determined that changes in the hemodynamics associated with leukoaraiosis, impaired cerebrovascular reserve, and intracranial hypoperfusion can lead to various clinical manifestations such as motor or cognitive impairment. The purpose of this study was to investigate the relationship between cognitive functional changes and imaging characteristics in patients with symptomatic leukoaraiosis, and to observe the corresponding changes in hemodynamics. Methods: A total of 203 Han patients (aged 43 - 93 years) with symptomatic leukoaraiosis were included in this study. Head magnetic resonance imaging was semi-quantified according to the Fazekas grading standard. Then, each patient was evaluated in terms of cognitive (Montreal scale) and executive function (trail-making test A [TMTA] and TMTB). Specifically, the TMTA asks patients to connect points on a piece of paper numbered from 1 to 25 in order and the TMTB asks patients to arrange numbers and letters in alternating order. In the current work, revised versions of these tests used are to include numbers in square and circular shapes where the shapes needed to be arranged in alternating order. The time required to complete the TMTA and TMTB was recorded. The changes in the blood flow velocity of the middle cerebral artery were also observed using routine Transcranial Doppler ultrasound and the breath-holding test. The dynamic curves of blood flow velocity during the breath-holding test were examined. Results: The cognitive and executive functions of patients with leukoaraiosis are related to the classification of image-based disease characteristics. In this sense, the more serious the leukoaraiosis is, the larger the impairment of cognitive and executive function is. According to the breath-holding test, the peak pattern of the blood flow velocity in the middle cerebral artery was significantly different between the various grades of leukoaraiosis. The peak type of Fazekas grade 0 and I w

关键词： leukoaraiosis Cerebral Hemodynamics Transcranial Doppler Ultrasound Breath-Holding Test Peak Type Middle Cerebral Artery Cognitive Function Executive Function

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Correlation of diffusion tensor imaging and cognitive function in patients with leukoaraiosis

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Neural Regeneration Research 2010年第15期5卷 1190-1195页

作者： Chuanqiang Qu Shougang Guo Hongzhi Guo Xiangshui Meng Chunjuan Wang Lin Ma Yan He Department of Radiology Qilu Hospital Affiliated to Shandong University Jinan 250012 Shandong Province China Department of Neurology Provincial Hospital Affiliated to Shandong University Jinan 250021 Shandong Province China Department of Neurology Qilu Hospital Affiliated to Shandong University Jinan 250012 Shandong Province China Department of Basic Medicine Shandong Medical College Jinan 250002 Shandong Province China Department of Neurology Second Hospital Affiliated to Shandong University of Traditional Chinese Medicine Jinan 250001 Shandong Province China

Conventional imaging technology does not measure white matter lesions of the brain or cognitive impairment. Diffusion tensor imaging is able to detect changes in the microstructure of white matter, and correlating vascular risk factors with cognitive dysfunction seems feasible using this technique. A total of 60 leukoaraiosis patients and 30 healthy elderly controls received diffusion tensor imaging examination to detect the average diffusion coefficient and fractional anisotropy of leukoaraiosis lesion and normal white matter. leukoaraiosis severity positively correlated with average diffusion coefficient but negatively correlated with fraction anisotropy. Neuropsychology tests （mini-mental state examination） were related to average diffusion coefficient and fraction anisotropy of normal white matter in leukoaraiosis patients, especially in the anterior horn and centrum semiovale. The average diffusion coefficient and fraction anisotropy of leukoaraiosis displayed characteristic changes. Therefore, diffusion tensor imaging can detect the macrostructural changes in white matter with normal magnetic resonance imaging, and these changes are related to cognitive function. Application of diffusion tensor imaging techniques to analyze the correlation between vascular risk factors and cognitive dysfunction is feasible.

关键词： diffusion tensor imaging cognitive function leukoaraiosis elderly magnetic resonance imaging neural regeneration

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Research progress on risk factors for leukoaraiosis

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Discussion of Clinical Cases 2017年第2期4卷 23-26页

作者： Shaojing Fu Dong Wang Weixing Huang Graduate School of Inner Mongolia Medical University HohhotInner MongoliaChina Department of Neurology The Third Affliated Hospital of Inner Mongolia Medical UniversityBaotouInner MongoliaChina

leukoaraiosis (LA), a term of neural imaging, is a disease which clinically causes cognitive dysfunction and gait disorders, eventually leads to persistent or progressive cognitive and neural dysfunction, seriously affects patients' daily lives. Early detection and identification of LA and its risk factors and early intervention may be of help to improve the quality of patients' living in the future. The research progress on risk factors for LA was reviewed in this study.

关键词： leukoaraiosis Risk factors Research progress

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DNA methylation profiling of leukoaraiosis:epigenetics of an emerging CNS neuro-inflammatory disorder

DNA methylation profiling of leukoaraiosis:epigenetics of an...

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中国神经科学学会第十届全国学术会议

作者： Wen-Qing HUANG Qing LIN Chi-Meng TZENG Translational Medicine Research Center School of Pharmaceutical SciencesXiamen University Department of Neurology The First Affiliated Hospital of Xiamen University

Objective leukoaraiosis（LA）,named as white matter lesions（WML）,is a common finding on magnetic resonance imaging（MRI） of the brain in elderly people with prevalence from 50 to 100%worldwide,mainly characterized by patchy demyelination,loss of oligodendroglial cells,axonal loss and denudation of the ependyma in regions of white matter hyperintensity.However,the mechanisms leading to the pathophysiology and neuroimaging abnormalities of the cerebral white matter have yet been poorly understood to date.Our approach is to identify an epigenetic basis for this complicated illness and further to decipher the pathogenic genes and its associated molecular mechanisms from the occurrence to the progression of LA through a deep going case-control study of LA.Methods All subjects were recruited in this study based on our new MRI-pathoimaging categorization of LA（Normal,Type Ⅰ LA,Type Ⅱ LA）.We conducted genome-scale methylation analysis among those three groups of subjects.Significantly methylation-associated genetic difference in both occurrence and progression of LA,were verified by pyrosequencing and further ontologically predicted into pathogenic mechanism/pathway.Results（1） As many as 152 and 198 genes were identified to show meaningful dissimilarity in the occurrence and progression of LA,respectively.Likewise,32genes were shared in between these two pathological processes.（2） Ontology analysis highlighted the epigenetic disruption in major mechanism of immune response（T-cell-,cytokine- and interferon-mediated signaling pathways）,neuron behaviors（development and interactive synaptic transmission/assembling） and cell performance（adhesion and apoptosis）.（3） Most meaningful methylation difference were validated by independent LA population（n=54）.Conclusion For the very first time,aberrant DNA methylation were reported,which are allied with both occurrence and progression of LA from Chinese population.Given that,most of LA-associated methylated genes and pathways were strongly associated with inflammatory development to fir

关键词： leukoaraiosis white matter lesions neuroimaging demyelination methylation inflammatory

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Vascular cognitive impairment, a cardiovascular complication

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世界精神病学杂志 2016年第2期6卷 199-207页

作者： Adiukwu Frances Ofori Sandra Ugbomah Lucy Department of Neuropsy- chiatry University of Port Harcourt Teaching Hospital Department of Internal Medicine University of Port Harcourt Teaching Hospital

Over the past two decades, the term vascular cognitive impairment(VCI) has been used to refer to a spectrum of cognitive decline characterized by executive dysfunction, associated with vascular pathology. With 30% of stroke survivors showing cognitive impairments, it is regarded as the most common cause of cognitive impairment. This is a narrative review of available literature citing sources from Pub Med, MEDLINE and Google Scholar. VCI has a high prevalence both before and after a stroke and is associated with great economic and caregiver burden. Despite this, there is no standardized diagnostic criteria for VCI. Hypertension has been identified as a risk factor for VCI and causes changes in cerebral vessel structure and function predisposing to lacuna infarcts and small vessel haemorrhages in the frontostriatal loop leading to executive dysfunction and other cognitive impairments. Current trials have shown promising results in the use of antihypertensive medications in the management of VCI and prevention of disease progression to vascular dementia. Prevention of VCI is necessary in light of the looming dementia pandemic. All patients with cardiovascular risk factors would therefore benefit from cognitive screening with screening instruments sensitive to executive dysfunction as well as prompt and adequate control of hypertension.

关键词： Vascular dementia leukoaraiosis White matter hyperintensities Cognitive screening Neurodegeneration

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A Study on the Correlation Between Cerebral Small Vascular Disease and Constitution Types of Traditional Chinese Medicine

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World Journal of Integrated Traditional and Western Medicine 2020年第11期6卷 7-14页

作者：王莲曾嵘冯浩丽李琳赵粮 Shanxi University of Chinese Medicine Taiyuan 030024China Department of Neurology Shanxi Provincial People's HospitalTaiyuan 030012China Department of Traditional Chinese Medicine Shanxi Provincial People's HospitalTaiyuan 030012China

Objective:To study the correlation between cerebral small vascular disease and constitution types of Traditional Chinese Medicine(TCM).Methods:The severity of lacunar infarction and leukoaraiosis were graded in 230 patients with cerebral small vascular disease,and they were divided into TCM constitution types.The survey of TCM constitution types was carried out by using standardized TCM constitution scale,and order multivariate Logistic regression was used to analyze the correlation between TCM constitution types with severity of lacunar infarction and leukoaraiosis.Results:Yang-deficiency(阳虚)constitution,blood-stasis constitution and phlegm-dampness constitution were the most common TCM constitution types in patients with lacunar infarction,accounting for 33.7%,12.5%,11.5%respectively.Yang-deficiency constitution,blood-stasis constitution and Yin-deficiency(阴虚)constitution were the most common TCM constitution types in patients with leukoaraiosis,accounting for 28.8%,18.5%,13.7%respectively.There were significant differences in lacunar infarction of Yang-deficiency constitution and blood stasis constitution(Pleukoaraiosis of phlegmdampness constitution and blood-stasis constitution(Pleukoaraiosis were age,smoking,hypertensive disease,phlegm-dampness constitution and blood-stasis constitution.The ordered multivariate Logistic regression analysis found that the severity of lacunar infarction was closely related to age,and the severity of leukoplosis was closely related to age,smoking and hypertension disease.Conclusion:TCM constitution types of lacunar infarction in patients with small cerebral vascular disease is mainly Yang-deficiency constitution and blood-stasis constitution,and the risk factors include age,smoking,alcohol consumption,Yang-deficiency cons

关键词： Cerebral small vascular diseas Lacunar infarction leukoaraiosis Constitutional types of traditional Chinese medicine Risk factors

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Predicting Mortality and Functional Outcomes after Ischemic Stroke: External Validation of a Prognostic Model

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Journal of Behavioral and Brain Science 2018年第10期8卷 587-597页

作者： Achala Vagal Heidi Sucharewv Christopher Lindsell Dawn Kleindorfer Kathleen Alwell Charles J. Moomaw Daniel Woo Matthew Flaherty Pooja Khatri Opeolu Adeoye Simona Ferioli Jason Mackey Sharyl Martini Felipe De Los Rios La Rosa F. Brett Kissela Departments of Radiology University of Cincinnati Medical Center Cincinnati OH USA Department of Biostatistics and Epidemiology Cincinnati Children’s Hospital Cincinnati OH USA Department of Emergency Medicine University of Cincinnati Medical Center Department of Neurology Cincinnati OH USA University of Cincinnati Medical Center Cincinnati OH USA Department of Neurology Indiana University School of Medicine Indianapolis Indiana USA Baylor College of Medicine Baptist Health Neuroscience Center Miami Florida USA

Background: We previously developed predictive models for 3-month mortality and modified Rankin Score (mRS) after ischemic stroke. Aim: The aim was to test model validity for 3-month mortality and mRS after ischemic stroke in two independent data sets. Methods: Our derivation models used data from 451 subjects with ischemic stroke in 1999 enrolled in the Greater Cincinnati/Northern Kentucky Stroke Study (GCKNSS). We utilized two separate cohorts of ischemic strokes through GCKNSS (460 in 2005 and 504 in 2010) to assess external validity by utilizing measures of agreement between predicted and observed values, calibration, and discrimination using Transparent Reporting of a multivariable prediction model for Individual Prognosis or Diagnosis. Results: The 3-month mortality model performed well in the validation datasets with an average prediction error (Brier score) of 0.045 for 2005 and 0.053 for 2010 and excellent discrimination with an area under the curve of 0.86 (95% CI: 0.79, 0.93) for 2005 and 0.84 (0.76, 0.92) for 2010. Predicted 3-month mRS also performed well in the validation datasets with R2 of 0.57 for 2005 and 0.50 for 2010 and a root mean square error of 0.85 for 2005 and 1.05 for 2010. Predicted mRS tended to be higher than actual in both validation datasets. Re-estimation of the model parameters for age and severe white matter hyperintensity in both 2005 and 2010, and for diabetes in 2005, improved predictive accuracy. Conclusions: Our previously developed stroke models performed well in two study periods, suggesting validity of the model predictions.

关键词： Ischaemic Stroke Epidemiology Stroke leukoaraiosis African American Stroke Prevalence

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